Highlights
- •Components of the Activins - Follistatins axis follow an opposite pattern of correlations for age and BMI vs. BMD
- •Follistatin (but not FSTL 3) and its ratios with activins are inversely associated with lumbar spine BMD
- •Follistatin (but not FSTL 3) and its ratios with activins are inversely associated with the presence of osteoporosis
- •Inhibin B levels were lower in postmenopausal osteoporotic women
Abstract
Background
Bone metabolism has been proposed to be affected by the activins-follistatins-inhibins
(AFI) hormonal system. We aimed to evaluate AFI in patients with osteoporosis and
osteopenia compared with postmenopausal and premenopausal controls.
Methods
In this case-control study, circulating levels of the AFI system were evaluated, individually
and jointly, between postmenopausal women with osteoporosis (BMD T-score ≤−2.5; n = 25)
or osteopenia (BMD T-score >−2.5 and ≤−1; n = 25) and postmenopausal women with normal
BMD (T-score >−1.0; n = 25) or premenopausal women with normal BMD (Z-score >−1.0;
n = 25), with and without adjustment for potential confounders.
Results
In the sum of participants, AFI molecules and their ratios followed an opposite pattern
of correlations for age and BMI vs. BMD. In unadjusted models, FSTL3 concentrations
were higher, whereas activin B, inhibin A and inhibin B and the ratios of activin
B/follistatin and activin B/FSTL3 were lower in the three postmenopausal groups compared
with the premenopausal group. Activin A/follistatin and activin AB/follistatin ratios
were lower in the osteoporosis group than the other three groups. After adjustment
for BMI and age, inhibin B (p = 0.005), and the ratios of activin A/follistatin (p = 0.009),
activin B/follistatin (p = 0.040) and activin AB/follistatin (p = 0.003) were lower
in the osteoporotic group compared with the other groups. In fully adjusted logistic
regression analysis log(inhibin B) (p = 0.041), log(activinA/follistatin) (p = 0.014),
log(activinB/follistatin) (p = 0.025) and log(activinAB/follistatin) (p = 0.021),
but not FSTL3, remained independently associated with the presence of osteoporosis.
Conclusions
Lower inhibin B and higher ratios of activins A, B, and AB to follistatin are associated
with lumbar spine BMD and the presence of osteoporosis independently from age or BMI.
Graphical abstract
Graphical Abstract
Abbreviations:
ActRIIA (activin receptor type IIA), AFI (activins-follistatins-inhibins system), BMD (bone mineral density), BMI (body mass index), FN (femoral neck), FSH (follicle-stimulating hormone), FSTL3 (follistatin-like 3), LS (lumbar spine), TGF-β (transforming growth factor-β)Keywords
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Article info
Publication history
Published online: December 29, 2022
Accepted:
December 26,
2022
Received:
October 6,
2022
Footnotes
☆Clinical Trials identifier: NCT04206618.
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.
